Polymer Films for Medical Device Coating

ABSTRACT

A method for depositing a coating comprising a polymer and impermeable dispersed solid on a substrate, comprising the following steps: discharging at least one impermeable dispersed solid in dry powder form through a first orifice; discharging at least one polymer in dry powder form through a second orifice; depositing the polymer and/or impermeable dispersed solid particles onto said substrate, wherein an electrical potential is maintained between the substrate and the impermeable dispersed solid and/or polymer particles, thereby forming said coating; and sintering said coating under conditions that do not disrupt the activity and/or function of the substrate. A similar method is provided for depositing a coating comprising a hydrophobic polymer and a water-vapor-trapping material on a substrate.

RELATED APPLICATIONS

This application claims the benefit of priority to U.S. ProvisionalPatent Application Ser. No. 60/940,365 filed May 25, 2007 and U.S.Provisional Patent Application Ser. No. 60/979,375 filed Oct. 11, 2007.The disclosure of these applications are incorporated herein byreference in their entirety.

BACKGROUND OF THE INVENTION

Medical devices often must be shielded from interacting with body fluidsin vivo. For example, for devices that are electrical in nature, forexample, such as pacemakers and other “active” implants for sensing,delivery of therapeutics and/or active control of various bodilyfunctions should be protected.

One prevalent method used to provide this protection is to weld thedevice inside a titanium or other biocompatible metal “can.” Anothermethod to provide the shield necessary to protect a medical device frominteraction with bodily fluids in vivo is polymer coating the device.Polymer coating such “active” implants has significant technicalchallenges and limitations which have made polymer coatings relativelyunsuccessful as a means of sealing the devices.

For example, one limitation of traditional coating processes inproviding a seal is that traditional polymer coating processes (e.g.dip, spray, etc.) all require the use of a solvent-based system.Exposing the device to a solvent causes problems in the device.Furthermore, there are inherent challenges with effective drying ofsolvent-based polymer coatings.

Solvent-less coating processes (e.g. vapor deposition, plasmadeposition, dry powder coating, etc.) also have limitations in providingseals to active devices. Solvent-less coating processes all require veryaggressive conditions that could damage the device—such as elevatedtemperatures to cure a dry powder coated device.

Additionally, for most current coating technologies, solvent-based andsolvent-less, it is often difficult to achieve coatings of uniformthicknesses and prevent the occurrence of defects (e.g. bare spots,webs, pools, clumps). As the size of the substrate decreases, and as themechanical complexity increases, it grows increasingly difficult touniformly coat all surfaces of a substrate. Supplemental steps,therefore, are sometimes necessary to assure proper coating, including,for example, multiple coating steps and/or drying between or after thecoating steps (in solvent-based systems).

Conventional polymer films likewise have limitations in providing aseal. Conventional polymer films are known to be quite ineffectivebarriers to the transport of gaseous materials. While this is especiallytrue of small molecule gases, the problem extends to providing a barrierto water vapors and other gases that could deleteriously effect anelectrical biomedical implant.

SUMMARY OF THE INVENTION

A cost-effective, easy to apply polymer-based coatings and coatingmethods to seal a substrate, where the collection process on thesubstrate is efficient, the coating produced is conformal, substantiallydefect-free and uniform, and the composition of the coating can beregulated and controlled is provided herein. The method and coatingsprovide a seal which is impermeable and/or imperveous to gas and/orfluid. The seal can be applied to a variety of substrates, including,but not limited to, implantable medical devices that are electrical innature such as pacemakers and other “active” implants, which can shieldthe substrates from interacting with body fluids in vivo.

The present invention relates to coatings and methods for depositing acoating comprising a polymer and a impermeable dispersed solid onto asubstrate. Provided herein are novel, easy to apply, polymer-basedcoatings and coating methods to seal and, thereby, shield, for example,medical devices that are electrical in nature such as pacemakers andother “active” implants from interacting with body fluids in vivo in amanner that disrupts the substrate's (e.g. active medical device's)intended functions and/or proper functioning, if any, or in a mannerthat has unintended consequences within and/or to the patient. Providedherein are novel, easy to apply, polymer-based coatings and coatingmethods to seal, for example, implantable medical devices that areelectrical in nature such as pacemakers and other “active” implants and,thereby, shield the body from degradation products, leachants, andextractables from the medical device. The coatings and methods providedherein result in a collection process on the substrate that isefficient, a conformal, substantially defect-free, and uniform coating,and a regulatable and controllable coating composition. The coatingstructures and methods provided herein not only avoid the problems ofpolymer coatings (solvent-based, and solvent-less), but they alsoimprove the barrier properties of polymer films for use as a seal upon,for example, biologically implanted devices.

Provided herein is a method for electrostatic capture of polymerparticles upon a substrate followed by sintering of these particles byexposure to compressed gasses. The coating methods used, includinge-RESS, e-SEDS, and/or eDPC are free from elevated temperatures, solventexposure, plasma environments, and other challenges associated withtraditional polymer coating methods.

In some embodiments, a coating comprising electrostatically capturedpolymer particles (generated by eRESS, eSEDS or eDPC) with eitherconcurrent or sequential captured impermeable particles (by eDFC, eRESS,eSEDS) on a medical implant substrate. A method is also provided forelectrostatically capturing polymer particles (generated by eRESS, eSEDSor eDPC) with either concurrent or sequential capturing impermeableparticles (by eDPC, eRESS, eSEDS) on a medical implant substrate.Following electrostatic capture of the impermeable particles and thepolymer, the method comprises sintering the medical implant substratewith a compressed gas at conditions adequate to cause flow of thepolymer particles into a continuous film on the substrate.

The polymers that could be used in the coatings or methods providedherein are all solution or thermally processible polymers (e.g.acrylates, olefins, fluoropolymers, urethanes, etc.). For example, apolymer (or polymers) could be used with known biocompatibility and highresistance to chemical degradation such as polymers of fluorinatedolefins. The impermeable particles that could be used in this coatingmethod includes all inorganic particles that can be obtained in themicron and/or sub-micron size range (for example, various compositionsof clay, metal-oxides, ceramics, etc.)

In one embodiment, a polymer coating is sufficient to provide therequisite sealing properties. In another embodiment, the coating wouldcontain a polymer continuous phase with particles embedded therein. Theexistence and distribution of the particles cases an increase in thebarrier properties of the film to small molecules and gases by blockingdiffusion pathways.

In some embodiments, the surface of the particles is chemically modifiedto provide greater dispersion and incorporation into the polymer film.In some embodiments of the method for coating, the method compriseschemically modifying the surface of the particles to provide greaterdispersion and incorporation into the polymer film. For example in thecase of a highly polar particle (e.g. clay, SiO2, TiO2, etc.) in ahighly non-polar polymer (e.g. polymeric fluorinated olefins), theprocess comprises binding or bonding a non-polar chemistry to thesurface of the particle prior to incorporation into the powder-coatingand sintering process.

Also, provided herein are stacked polymer films with an interveningimpermeable layer which could provide similar protection for sensitivedevices in vivo without the difficulty associated with welding metalcans around the device. In some embodiments, polymers to be used in theprocesses and in the coatings provided herein are inherentlyhydrophobic, thereby greatly reducing the likelihood of penetration ofbiological fluids. For example, fluoropolymers as a class yield highsurface energy surfaces that meet this requirement. However, surfacescreated from such polymers in some cases act as membranes through whichwater vapor transport can occur. Thus, in some embodiments, a secondlayer that can trap any water vapor that might permeate thefluoropolymer membrane is provided. In some embodiments, the methodcomprises depositing a hydrophilic polymer layer such as a silicon basedpolymer over the initial fluoropolymer layer. Silicon based polymers canbe designed to possess differing degrees of hydrophilicity and thereforetrap any water vapor that might permeate the fluoropolymer layermembrane. In some embodiments, the silicon-based polymer is reduced tonative silicon and metallized with titanium. In some embodiments, athird layer of fluoropolymer is deposited to encapsulate the siliconbased polymer layer between the fluoropolymer layers. In someembodiments, the coating comprises multiple alternating layers offluoropolymers and silicon based polymers. In some embodiments, themethod comprises alternating multiple layers of the silicon basedpolymer and the fluoropolymer.

In some embodiments, the coating is designed to remain impermeableand/or impervious to gas and/or fluid for at least as long as theexpected life span (e.g., period of time inside a subjects body) of thedevice and/or substrate it coats.

One aspect of the invention provides methods for depositing a coatingcomprising a polymer and impermeable dispersed solid on a substrate,comprising discharging at least one impermeable dispersed solid in drypowder form through a first orifice; discharging at least one polymer indry powder form through a second orifice; depositing the polymer and/orimpermeable dispersed solids onto said substrate, wherein an electricalpotential is maintained between the substrate and the impermeabledispersed solid and/or polymer particles, thereby forming said coating;and sintering said coating under conditions that do not substantiallyaffect the substrate. In some embodiments, the impermeable dispersedsolid is dispersed uniformly on all exposed surfaces of the substrate.In some embodiments, the impermeable dispersed solid is impermeableand/or impervious to gas. In some embodiments, the impermeable dispersedsolid is impermeable and/or impervious to fluid. In some embodiments,the impermeable dispersed solid is impermeable and/or impervious tobiological material.

In some embodiments, the impermeable dispersed solid comprisesnanoparticles, such as, for example, a polyurethane adhesivenanocomposite (organically modified montmorillonite and polyurethane).In some embodiments, the oxygen transmission rate across the coating isat most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In someembodiments the water vapor permeation through the coating is at mostabout 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In referring totransmission rate or permeation, “about” refers to variations of 0.01%to 0.1%, or 1% to 5%.

Although the size, resistivity and moisture content of the polymer andimpermeable dispersed solid may vary widely based on the conditionsused, desired particle sizes are typically in the range of 0.01 μm-2500μm, and more preferably in the range of 0.01 μm-100 μm, resistivity istypically in the range of from about 106 Ωm to about 1024 Ωm andmoisture content is less than 5% by weight. In one embodiment of theinvention the molecular weight range of the polymer is from about 5,000a.u. to about 100,000 a.u.

In other embodiments, the first and second orifices are provided as onesingle orifice wherein the impermeable dispersed solid and polymer maybe mixed together prior to discharging. In yet other embodiments theimpermeable dispersed solid and polymer particles may be dischargedsimultaneously or in succession. In another embodiment of the inventionthe method further comprises discharging a third dry powder comprising asecond impermeable dispersed solid whereby a coating comprising at leasttwo different impermeable dispersed solids is deposited on saidsubstrate. In certain other embodiments of the invention the impermeabledispersed solid is prepared by milling, jet-milling, granulation, spraydrying, crystallizing or fluidizing.

In a further embodiment the impermeable dispersed solid and/or thepolymer becomes electrostatically charged prior to deposition, and thesubstrate may be electrically grounded. In a preferred embodiment, thesubstrate is electrostatically charged. In some embodiments the polymerand impermeable dispersed solid are discharged using a gas basedpropellant, which typically comprises carbon dioxide, nitrous oxide,hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressedair, argon, or volatile hydrocarbons with a vapor pressure greater than750 Torr at 20° C., and is preferably carbon dioxide.

In one embodiment of the invention the impermeable dispersed solidcomprises at least one drug. In another embodiment of the invention theratio of impermeable dispersed solid to polymer is from about 1:1000 toabout 3:10. In some embodiments, the amount of impermeable dispersedsolid will depend on the particular dispersed solid being employed, thetype of substrate, and the medical condition being treated.

Yet another aspect of the invention provides methods for depositing acoating comprising a polymer and a impermeable dispersed solid on asubstrate, comprising discharging at least one impermeable dispersedsolid in a therapeutically desirable morphology in dry powder formthrough a first orifice; forming a supercritical or near supercriticalfluid mixture that includes at least one supercritical fluid solvent andat least one polymer and discharging said supercritical or nearsupercritical fluid solution through a second orifice under conditionssufficient to form solid particles of the polymer; depositing thepolymer and/or impermeable dispersed solids onto said substrate, whereinan electrical potential is maintained between the substrate and theimpermeable dispersed solids and/or polymer particles, thereby formingsaid coating and sintering said coating under conditions that do notsubstantially disrupt the substrate's (e.g. active medical device's)intended functions and proper functioning, if any, or that haveunintended consequences within and/or to the patient once implanted.

Each of the above methods may be carried out from about 0° C. to about80° C. and from about 0.1 atmospheres to about 73 atmospheres, in eitheropen or closed vessel. In some embodiments, the substrate is abiomedical implant which may be a. a stent (e.g., vascular stents),electrode, catheter, lead, implantable pacemaker, implantablecardioverter, a housing for an implantable pacemaker, a housing for animplantable defibrillator, a housing for an implantable cardioverter,sensor, drug delivery device, therapy delivery device, device comprisingtelemetry capability, device comprising electrical impulses, diagnosticdevice, measurement device, joint, screw, rod, ophthalmic implant,femoral pin, bone plate, graft, anastomotic device, perivascular wrap,suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bagattachment device, ear drainage tube, lead for pace makers andimplantable cardioverters and defibrillators, vertebral disk, bone pin,suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascularimplant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmicimplant, prosthetic, shunt, urologic implant, reproductive anatomydevice, gastrologic device, neurologic lead, neurologic device, varioustypes of dressings (e.g., wound dressings), bone substitutes,intraluminal devices, and vascular supports.

In some embodiments of the invention the thickness of said coating isfrom about 1 to about 100 μm, preferably about 10 μm, and the variationin the thickness along said coating is within 0.5 μm, within 0.25 μm,within 0.1 μm or within 10% of the total thickness of said coating,within 5% of the total thickness of said coating, or within 2.5% of thetotal thickness of said coating. In yet other embodiments, theimpermeable dispersed solid is positioned at a selected distance fromtop of said coating. In further embodiments, the impermeable dispersedsolid is positioned at about midway between the top of said coating andthe substrate surface. In other embodiments of the invention thevariability in the amount of impermeable dispersed solid deposited onsaid substrate is 20% or less, 15% or less, 10% or less, 5% or less, fora batch of substrates coated at the same time. Preferably thevariability is 5% or less.

In yet other embodiments of the invention, the methods further comprisedepositing a top layer on said coating wherein said top layer is apolymer film. In some embodiments, the polymer film has a thickness of0.5 to 10 microns, and can be deposited by an eRESS or eSEDS, or a eDPCprocess. In yet other embodiments, the polymer film is formed bydepositing a single polymer and for example by depositing substantiallypure PBMA.

The invention further relates to the use of a supercritical solutioncomprising a second fluid in its supercritical state.

In some embodiments, the addition of a second fluid in its supercriticalstate is to act as a flammability suppressor. In other embodiments, asecond fluid is used, wherein said second fluid has critical parameterslower than the first fluid's critical parameters, and therefore lowersthe critical properties of the mixture/solution enabling access to themixture supercritical state.

In some embodiments the supercritical solution comprises isobutylene. Inother embodiments, the supercritical fluid comprises isobutylene andcarbon dioxide as a second fluid.

Other embodiments of the invention provide a way to dissolve twopolymers in a supercritical solvent.

In some embodiments said two polymers are PEVA and PBMA. In otherembodiments, a supercritical solution comprising two polymers is used tocreate a RESS spray of the polymers generating ˜10 to 100 nm particlesof each polymer. In further embodiments, PEVA and PBMA are dissolved ina supercritical solvent that further comprises CO₂ to act as a firesuppressor in the event of an ignition source causing a fire.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended Claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1. Schematic Representation of the Coating and Sintering ProcessApparatus.

FIG. 2. Detailed images of the Coating and Sintering Process Apparatus.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is explained in greater detail below. Thisdescription is not intended to be a detailed catalog of all thedifferent ways in which the invention may be implemented, or all thefeatures that may be added to the instant invention. For example,features illustrated with respect to one embodiment may be incorporatedinto other embodiments, and features illustrated with respect to aparticular embodiment may be deleted from that embodiment. In addition,numerous variations and additions to the various embodiments suggestedherein will be apparent to those skilled in the art in light of theinstant disclosure, which do not depart from the instant invention.Hence, the following specification is intended to illustrate someparticular embodiments of the invention, and not to exhaustively specifyall permutations, combinations and variations thereof.

Applicants specifically intend that all United States patent referencescited herein be incorporated herein by reference in their entirety.

The present invention relates to coatings and methods for depositing acoating comprising a polymer and a impermeable dispersed solid onto asubstrate. Provided herein are novel, easy to apply, polymer-basedcoatings and coating methods to seal and, thereby, shield, for example,implantable medical devices that are electrical in nature such aspacemakers and other “active” implants from interacting with body fluidsin vivo in a manner that disrupts the medical device's intendedfunctions and proper functioning, or in a manner that has unintendedconsequences within and/or to the patient. Provided herein are novel,easy to apply, polymer-based coatings and coating methods to seal, forexample, implantable medical devices that are electrical in nature suchas pacemakers and other “active” implants and, thereby, shield the bodyfrom degradation products, leachants, extractables from the medicaldevice. The coatings and methods provided herein result in a collectionprocess on the substrate that is an efficient, conformal, substantiallydefect-free, and uniform coating, and a regulatable and controllablecoating composition. The coating structures and methods provided hereinnot only avoid the problems of polymer coatings (solvent-based, andsolvent-less), but they also improve the barrier properties of polymerfilms for use as a seal upon, for example, biologically implanteddevices.

Provided herein is a composite material coating containing polymer toprovide increased barrier properties for gases such as water vapor, andmethod of creating such coating.

Provided herein is a composite material coating containing polymer plusa impermeable dispersed solid to provide increased barrier propertiesfor gases such as water vapor, and method of creating such coating.

Provided herein is the a method for electrostatic capture of polymerparticles upon a substrate followed by sintering of these particles byexposure to compressed gasses. The coating methods used, includinge-RESS, e-SEDS, and/or eDPC are free from elevated temperatures, solventexposure, plasma environments, and other challenges associated withtraditional polymer coating methods.

In some embodiments, a coating comprising electrostatically capturedpolymer particles (generated by eRESS, eSEDS or eDPC) alone oroptionally with either concurrent or sequential captured impermeableparticles (by eDPC, eRESS, eSEDS) on a medical implant substrate. Amethod is also provided for electrostatically capturing polymerparticles (generated by eRESS, eSEDS or eDPC) alone or with eitherconcurrent or sequential capturing impermeable particles (by eDPC,eRESS, eSEDS) on a medical implant substrate. Following electrostaticcapture of the polymer and optionally impermeable particles, the methodcomprises sintering the medical implant substrate with a compressed gasat conditions adequate to cause flow of the polymer particles into acontinuous film on the substrate.

The polymers that could be used in the coatings or methods providedherein are all solution or thermally processible polymers (e.g.acrylates, olefins, fluoropolymers, urethanes, etc.). For example, apolymer (or polymers) could be used with known biocompatibility and highresistance to chemical degradation such as polymers of fluorinatedolefins. The impermeable particles that could be used in this coatingmethod includes all inorganic particles that can be obtained in themicron and/or sub-micron size range. For example various compositions ofclay, metal-oxides, ceramics, etc.

The resulting film would contain a polymer continuous phase optionallywith particles embedded therein. The existence and distribution of theparticles causes an increase in the barrier properties of the film tosmall molecules and gases by blocking diffusion pathways.

In some embodiments of the coating, the surface of the particles ischemically modified to provide greater dispersion and incorporation intothe polymer film. In some embodiments of the method for coating, themethod comprises chemically modifying the surface of the particles toprovide greater dispersion and incorporation into the polymer film. Forexample in the case of a highly polar particle (e.g. clay, SiO2, TiO2,etc.) in a highly non-polar polymer (e.g. polymeric fluorinatedolefins), the process comprises binding or bonding a non-polar chemistryto the surface of the particle prior to incorporation into thepowder-coating and sintering process.

Provided herein are stacked polymer films with an interveningimpermeable layer which could provide similar protection for sensitivedevices in vivo without the difficulty associated with welding metalcans around the device. In some embodiments, polymers to be used in theprocesses and in the coatings provided herein are inherentlyhydrophobic, thereby greatly reducing the likelihood of penetration ofbiological fluids. For example, fluoropolymers as a class yield highsurface energy surfaces that meet this requirement. However, surfacescreated from such polymers in some cases act as membranes through whichwater vapor transport can occur. Thus, in some embodiments, a secondlayer that can trap any water vapor that might permeate thefluoropolymer membrane is provided. In some embodiments, the methodcomprises depositing a hydrophilic polymer layer such as a silicon basedpolymer over the initial fluoropolymer layer. Silicon based polymers canbe designed to possess differing degrees of hydrophilicity and thereforetrap any water vapor that might permeate the fluoropolymer layermembrane. In some embodiments, the silicon-based polymer is reduced tonative silicon and metallized with titanium.

In some embodiments, a highly absorbent material is used as thewater-vapor trapping material. In some embodiments, the highly absorbentmaterial comprises a hydrophilic polymer. In some embodiments, highlyabsorbent material comprises a superabsorbent polymer.

In some embodiments, a third layer of fluoropolymer is deposited toencapsulate the silicon based polymer layer between the fluoropolymerlayers. In some embodiments, the coating comprises multiple alternatinglayers of fluoropolymers and silicon based polymers. In someembodiments, the method comprises alternating multiple layers of thesilicon based polymer and the fluoropolymer.

In some embodiments, the coating is designed to remain impermeable forat least as long as the expected life span of the device and/orsubstrate it coats.

One aspect of the invention provides methods for depositing a coatingcomprising a polymer and impermeable dispersed solid on a substrate,comprising discharging at least one impermeable dispersed solid in drypowder form through a first orifice; discharging at least one polymer indry powder form through a second orifice; depositing the polymer and/orimpermeable dispersed solids onto said substrate, wherein an electricalpotential is maintained between the substrate and the impermeabledispersed solid and/or polymer particles, thereby forming said coating;and sintering said coating under conditions that do not substantiallyaffect the substrate. In some embodiments, the impermeable dispersedsolid is dispersed uniformly on all exposed surfaces of the substrate.

In some embodiments, the impermeable dispersed solid comprises ananoparticle, such as, for example, a polyurethane adhesivenanocomposite (organically modified montmorillonite and polyurethane).In some embodiments, the oxygen transmission rate across the coating isat most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In someembodiments the water vapor permeation through the coating is at mostabout 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In referring totransmission rate or permeation, “about” refers to variations of 0.01%to 0.1%, or 1% to 5%.

In some embodiments, the impermeable dispersed solid comprises ananoparticle that is impervious to small particle transport. In someembodiments, the nanoparticle comprises at least one of a ceramic and ametal. In some embodiments, the nanoparticle comprises clay. In someembodiments the nanoparticle comprises silica. In some embodiments, thenanoparticle comprises titanium oxide. In some embodiments, thenanoparticle does not include nickel. In some embodiments, thenanoparticle does not include copper. In some embodiments, the smallparticle transmission rate across the coating is at most about 0.001%,0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In someembodiments, the oxygen transmission rate across the coating is at mostabout 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.In some embodiments the water vapor permeation through the coating is atmost about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or70%. In referring to transmission rate or permeation, “about” refers tovariations of 0.001% to 0.01%, 0.01% to 0.1%, or 1% to 5%.

Although the size, resistivity and moisture content of the polymer andimpermeable dispersed solid may vary widely based on the conditionsused, desired particle sizes are typically in the range of 0.01 μm-2500μm, and more preferably in the range of 0.01 μm-100 μm, resistivity istypically in the range of from about 106 Ωm to about 1024 Ωm andmoisture content is less than 5% by weight. In one embodiment of theinvention the molecular weight range of the polymer is from about 5,000a.u. to about 100,000 a.u.

In other embodiments, the first and second orifices are provided as onesingle orifice wherein the impermeable dispersed solid and polymer maybe mixed together prior to discharging. In yet other embodiments theimpermeable dispersed solid and polymer particles may be dischargedsimultaneously or in succession. In another embodiment of the inventionthe method further comprises discharging a third thy powder comprising asecond impermeable dispersed solid whereby a coating comprising at leasttwo different impermeable dispersed solids is deposited on saidsubstrate. In certain other embodiments of the invention the impermeabledispersed solid is prepared by milling, jet-milling, granulation, spraydrying, crystallizing or fluidizing.

In a further embodiment the impermeable dispersed solid and/or thepolymer becomes electrostatically charged prior to deposition, and thesubstrate may be electrically grounded. In a preferred embodiment, thesubstrate is electrostatically charged. In some embodiments the polymerand impermeable dispersed solid are discharged using a gas basedpropellant, which typically comprises carbon dioxide, nitrous oxide,hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressedair, argon, or volatile hydrocarbons with a vapor pressure greater than750 Torr at 20° C., and is preferably carbon dioxide.

In one embodiment of the invention the impermeable dispersed solidcomprises at least one drug. In another embodiment of the invention theratio of impermeable dispersed solid to polymer is from about 1:1000 toabout 3:10. In some embodiments, the amount of impermeable dispersedsolid will depend on the particular dispersed solid being employed, thetype of substrate, and the medical condition being treated.

Yet another aspect of the invention provides methods for depositing acoating comprising a polymer and a impermeable dispersed solid on asubstrate, comprising discharging at least one a impermeable dispersedsolid in a therapeutically desirable morphology in dry powder formthrough a first orifice; forming a supercritical or near supercriticalfluid mixture that includes at least one supercritical fluid solvent andat least one polymer and discharging said supercritical or nearsupercritical fluid solution through a second orifice under conditionssufficient to form solid particles of the polymer; depositing thepolymer and/or impermeable dispersed solids onto said substrate, whereinan electrical potential is maintained between the substrate and theimpermeable dispersed solids and/or polymer particles, thereby formingsaid coating and sintering said coating under conditions that do notsubstantially disrupt the substrate's (e.g. implantable active medicaldevice's) intended functions and proper functioning, if any, or thathave unintended consequences within and/or to the patient onceimplanted.

Each of the above methods may be carried out from about 0° C. to about80° C. and from about 0.1 atmospheres to about 73 atmospheres, in eitheropen or closed vessel. In some embodiments, the substrate is a stent(e.g., vascular stents), electrode, catheter, lead, implantablepacemaker, implantable cardioverter, a housing for an implantablepacemaker, a housing for an implantable defibrillator, a housing for animplantable cardioverter, sensor, drug delivery device, therapy deliverydevice, device comprising telemetry capability, device comprisingelectrical impulses, diagnostic device, measurement device, joint,screw, rod, ophthalmic implant, femoral pin, bone plate, graft,anastomotic device, perivascular wrap, suture, staple, shuntsforhydrocephalus, dialysis graft, colostomy bag attachment device, eardrainage tube, lead for pace makers and implantable cardioverters anddefibrillators, vertebral disk, bone pin, suture anchor, hemostaticbarrier, clamp, screws, plate, clip, vascular implant, tissue adhesive,sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt,urologic implant, reproductive anatomy device, gastrologic device,neurologic lead, neurologic device, various types of dressings (e.g.,wound dressings), bone substitutes, intraluminal devices, and vascularsupports.

In some embodiments of the invention the thickness of said coating isfrom about 1 to about 100 μm, preferably about 10 μm, and the variationin the thickness along said coating is within 0.5 μm, within 0.25 μm,within 0.1 μm or within 10% of the total thickness of said coating,within 5% of the total thickness of said coating, or within 2.5% of thetotal thickness of said coating. In yet other embodiments, theimpermeable dispersed solid is positioned at a selected distance fromtop of said coating. In further embodiments, the impermeable dispersedsolid is positioned at about midway between the top of said coating andthe substrate surface. In other embodiments of the invention thevariability in the amount of impermeable dispersed solid deposited onsaid substrate is 20% or less, 15% or less, 10% or less, 5% or less, fora batch of substrates coated at the same time. Preferably thevariability is 5% or less.

In yet other embodiments of the invention, the methods further comprisedepositing a top layer on said coating wherein said top layer is apolymer film. In some embodiments, the polymer film has a thickness of0.5 to 10 microns, and can be deposited by an eRESS or eSEDS, or a eDPCprocess. In yet other embodiments, the polymer film is formed bydepositing a single polymer and can be formed by depositingsubstantially pure PBMA.

The invention further relates to the use of a supercritical solutioncomprising a second fluid in its supercritical state.

In some embodiments, the addition of a second fluid in its supercriticalstate is to act as a flammability suppressor. In other embodiments, asecond fluid is used, wherein said second fluid has critical parameterslower than the first fluid's critical parameters, and therefore lowersthe critical properties of the mixture/solution enabling access to themixture supercritical state.

In some embodiments the supercritical solution comprises isobutylene. Inother embodiments, the supercritical fluid comprises isobutylene andcarbon dioxide as a second fluid.

Other embodiments of the invention provide a way to dissolve twopolymers in a supercritical solvent. In some embodiments said twopolymers are PEVA and PBMA. In other embodiments, a supercriticalsolution comprising two polymers is used to create a RESS spray of thepolymers generating ˜10 to 100 nm particles of each polymer. In furtherembodiments, PEVA and PBMA are dissolved in a supercritical solvent thatfurther comprises CO₂ to act as a fire suppressor in the event of anignition source causing a fire.

One aspect of the invention entails the deposition of the a impermeabledispersed solid as dry powders, using electrostatic capture to attractthe powder particles to the substrate. Dry powder spraying is well knownin the art, and dry powder spraying coupled with electrostatic capturehas been described, for example in U.S. Pat. No. 5,470,603 6,319,541 or6,372,246. The deposition of the polymer can be performed in any numberof standard procedures, as the morphology of the polymer, so long as itprovides coatings possessing the desired properties (e.g. thickness,conformity, defect-free, uniformity), and are free from elevatedtemperatures, solvent exposure, plasma environments, and otherchallenges associated with traditional polymer coating methods.

The second step of the coating process involves taking the substratesthat have been coated with impermeable dispersed solids and polymers andsubjecting them to a sintering process that takes place under conditionsfree from elevated temperatures, solvent exposure, plasma environments,and other challenges associated with traditional polymer coatingmethods. The sintering process as used in the current invention refersto the process by which the co-deposited impermeable dispersedsolid—polymer matrix become fused and adherent to the substrate bytreatment of the coated substrate with a compressed gas, compressedliquid, or supercritical fluid that is a non-solvent for the polymersand the impermeable dispersed solid(s), but a plasticizing agent for thepolymer. The sintering process takes place under conditions (e.g. mildtemperatures), and using benign fluids (e.g. supercritical carbondioxide) which will not affect the active substrate or its subsequentfunction, if any.

One aspect of the invention is the combination of two or more of thee-DPC, e-RESS and e-SEDS spraying techniques.

A specific aspect of the invention involves the dry powder spraying ofimpermeable dispersed solid, in a preferred particle size, into the samecapture vessel as a polymer that is also dry powder sprayed, whereby thespraying of the impermeable dispersed solid and the polymer issequential or simultaneous.

In some embodiments, the invention involves the e-DPC spraying of theimpermeable dispersed solid, into the same capture vessel as a polymerthat is sequentially or simultaneously sprayed by the eRESS sprayprocess. In some embodiments, the invention involves the e-DPC sprayingof the impermeable dispersed solid, into the same capture vessel as apolymer that is sequentially or simultaneously sprayed by the eSEDSspray process. In some embodiments, the invention involves the e-DPCspraying of the impermeable dispersed solid, into the same capturevessel as a polymer that is sequentially or simultaneously sprayed bythe eDPC spray process.

In some embodiments, the invention involves the e-RESS spraying of theimpermeable dispersed solid, into the same capture vessel as a polymerthat is sequentially or simultaneously sprayed by the eRESS sprayprocess. In some embodiments, the invention involves the e-RESS sprayingof the impermeable dispersed solid, into the same capture vessel as apolymer that is sequentially or simultaneously sprayed by the eSEDSspray process. In some embodiments, the invention involves the e-RESSspraying of the impermeable dispersed solid, into the same capturevessel as a polymer that is sequentially or simultaneously sprayed bythe eDPC spray process.

In some embodiments, the invention involves the e-SEDS spraying of theimpermeable dispersed solid, into the same capture vessel as a polymerthat is sequentially or simultaneously sprayed by the eRESS sprayprocess. In some embodiments, the invention involves the e-SEDS sprayingof the impermeable dispersed solid, into the same capture vessel as apolymer that is sequentially or simultaneously sprayed by the eSEDSspray process. In some embodiments, the invention involves the e-SEDSspraying of the impermeable dispersed solid, into the same capturevessel as a polymer that is sequentially or simultaneously sprayed bythe eDPC spray process.

Any combination of the above processes is contemplated by this aspect ofthe invention.

In further aspects of the invention the substrates that have been coatedwith impermeable dispersed solid and polymers, as described in the aboveembodiments are then subjected to a sintering process. The sinteringprocess takes place under conditions free from elevated temperatures,solvent exposure, plasma environments, and other challenges associatedwith traditional polymer coating methods, and refers to a process bywhich the co-deposited impermeable dispersed solid-polymer matrix,becomes fused and adherent to the substrate. This is achieved bytreating the coated substrate with a compressed gas, compressed liquidor supercritical fluid that is a non-solvent for the polymers, theimpermeable dispersed solids, but a plasticizing agent for the polymer.The sintering process takes place under conditions (e.g. mildtemperatures), and using benign fluids (e.g. supercritical carbondioxide) which will not affect the active substrate or its subsequentfunction, if any. Other sintering processes, which do not affect theactive substrate or its subsequent function, if any may also becontemplated by the present invention.

DEFINITIONS

As used in the present specification, the following words and phrasesare generally intended to have the meanings as set forth below, exceptto the extent that the context in which they are used indicatesotherwise.

“Substrate” as used herein, refers to any surface upon which it isdesirable to deposit a coating comprising a polymer or a mix of polymerwith or without impermeable dispersed solid, or hydrophobic polymers anda water-vapor-trapping material, wherein the coating process does notsubstantially disrupt the substrate's (e.g. implantable active medicaldevice's) intended functions and/or proper functioning, if any, or in amanner that has unintended consequences within and/or to the patient.Biomedical implants are of particular interest for the presentinvention; however the present invention is not intended to berestricted to this class of substrates. Those of skill in the art willappreciate alternate substrates that could benefit from the coatingprocess described herein, such as temporary implantable devices,diagnostic tests or kits.

“Biomedical implant” as used herein refers to any implant for insertioninto the body of a human or animal subject, including but not limited toa stent (e.g., vascular stents), electrode, catheter, lead, implantablepacemaker, implantable cardioverter, a housing for an implantablepacemaker, a housing for an implantable defibrillator, a housing for animplantable cardioverter, sensor, drug delivery device, therapy deliverydevice, device comprising telemetry capability, device comprisingelectrical impulses, diagnostic device, measurement device, joint,screw, rod, ophthalmic implant, femoral pin, bone plate, graft,anastomotic device, perivascular wrap, suture, staple, shuntsforhydrocephalus, dialysis graft, colostomy bag attachment device, eardrainage tube, lead for pace makers and implantable cardioverters anddefibrillators, vertebral disk, bone pin, suture anchor, hemostaticbarrier, clamp, screws, plate, clip, vascular implant, tissue adhesive,sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt,urologic implant, reproductive anatomy device, gastrologic device,neurologic lead, neurologic device, various types of dressings (e.g.,wound dressings), bone substitutes, intraluminal devices, and vascularsupports, etc.

The implants may be formed from any suitable material, including but notlimited to organic polymers (including stable or inert polymers andbiodegradable polymers), metals, inorganic materials such as silicon,and composites thereof, including layered structures with a core of onematerial and one or more coatings of a different material.

Subjects into which biomedical implants of the invention may be appliedor inserted include both human subjects (including male and femalesubjects and infant, juvenile, adolescent, adult and geriatric subjects)as well as animal subjects (including but not limited to dog, cat,horse, monkey, etc.) for veterinary purposes.

In a preferred embodiment the biomedical implant is an implantablepacemaker, cardioverter or defibrillator, or another active device orany implantable (permanent or temporary) device requiring sealing toprevent gas or fluid permeation.

“Active” or “Active medical device” as used herein refers to medicaldevices that are electrical in nature, such as pacemakers and othermedical devices for sensing, delivery of therapeutics and/or activecontrol of various bodily functions.

“Medical device” as used herein can refer to biological implants asdefined herein active or inactive. A medical device may be permanentlyimplantable, temporarily implantable, entirely implantable (such as, forexample, an implantable defibrillator), partially implantable (such as,for example, a sensing drainage catheter) and/or can refer to devicesused on or in a patient during a diagnostic or therapeutic procedure,including during an invasive surgery or during a minimally invasivesurgery. A medical device includes any instrument, apparatus, appliance,material or other article, whether used alone or in combination,including any software necessary for its proper application intended bythe manufacturer to be used for human beings for the purpose of:diagnosis, prevention, monitoring, treatment or alleviation of disease,alleviation of pain, diagnosis, monitoring, treatment, alleviation of orcompensation for an injury or handicap, investigation, replacement ormodification of the anatomy or of a physiological process, control ofconception, and which does not achieve its principal intended action inor on the human body by pharmacological, immunological or metabolicmeans, but which may be assisted in its function by such means. Forexample, an insulin pump implanted in a diabetic person which dispensesinsulin stored in the pump into the patient's blood based upon glucoselevels sensed by the pump is a medical device (and is an active medicaldevice and a biological implant).

“Biological material” as used herein can refer a biological material ingas or fluid state including small solid particles.

“Defect” as used herein can refer to, but is not limited to: surfacetopology variability, such as a clump, a web, or a pool; a through-layerdeficiency, such as a bare spot, a fracture, a crack, a pin hole, a thinspot, a blemish; or a under-layer defect, such as a bubble betweenlayers, a bubble beneath a layer, matter trapped beneath a layer orbetween layers of coating which is not a part of the substrate or of thelayer(s), such as dust, liquid, gas, or particulate, An under-layerdefect might affect the seal of a substrate device. For example, anunder-layer water vapor bubble might act as a sink for diffusion ofwater vapor, making an active device more prone to interacting with thevapor and/or potentially with body fluids in vivo in a manner thatdisrupts the substrate's (e.g. active device's) intended functionsand/or proper functioning, if any, or in a manner that has unintendedconsequences within and/or to the patient. Likewise, any other defect(through-layer, or surface topology variability) which allows gas orfluids to interact with the substrate can potentially result indisruption of the substrate's (e.g. active device's) intended functionsand/or proper functioning, if any, or in a manner that has unintendedconsequences within and/or to the patient (such as, for a non-limitingexample, freeing leachables, and/or creating or releasing degradationproducts or extractables from the device and into the body of thepatient).

“Conformal coating”, “conformally coated”, or “conformably coated” asused herein can refer to a protective covering that conforms to theconfiguration of the objects coated. A covering that is conformal coverssusbtantially all surfaces with a uniform layer. For example, a coatinglayering process may confomally coat a device with a 10 micron coating(of a layer or of layers) plus or minus 10%, which results in a 10micron plus or minus 10% coating on every external surface of the devicethat is at least about 20 microns apart from another external surface ofthe device (external surfaces of the device that are closer may appearto have thicker coatings as the coatings on of the two nearby surfacesjoin).

“Seal” or “Substantially seal” as used herein can refer to coating thatsubstantially shields a substrate from interacting with materials(fluids, gases, solids), in a manner that disrupts the substrate'sintended functions and/or proper functioning, if any, or in a mannerthat has unintended consequences within and/or to the patient. As usedherein, the term(s) can refer to coating that substantially shieldstransmission of degradation products, leachants, and extractables fromthe substrate past and/or through the coating. Seals on a substrate canbe applied to electronic circuitry to act as protection for thecircuitry against, for example, moisture, dust, chemicals, and/ortemperature extremes. Similarly, seals can be applied to devices to actas protection against, for example, moisture, dust, chemicals,leachants, extractable components (extractables) and/or degradationproducts, from passing from the device through the coating layer(s). Aseal, therefore can be a one-way and/or two-way barrier to moisture,dust, chemicals, leachants, degradation products, and/or other material(fluid or gas), including biologic material. The one-way barrier can bea barrier in either direction, a barrier to allowing material to contactthe substrate, or a barrier to allowing material to pass from thesubstrate through the coating for example to the blood stream of asubject. For example, a medical device that is electrical in nature suchas a pacemaker and/or another “active” implant body fluids in vivo canbe substantially sealed by a coating and, thereby, substantiallyshielded from interacting with materials (fluids, gases, solids), in amanner that disrupts the substrate's intended functions and/or properfunctioning, if any, or in a manner that has unintended consequenceswithin and/or to the patient. Medical devices that are not electrical innature (or not primarily electrical in nature) may also be sealed asprovided herein. “Substantially” where used herein with respect tosealing or seals, can mean at least about one of 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5% 99.6%, 99.7%, 99.8%, 99.9%, 99.95%, 99.99%, and99.995% sealed. “About” where used herein with respect to sealing orseals percentages, can mean variability of 0.1 to 0.5%, or 1-5%.“Substantially” where used herein with respect to sealing or seals, canalso or alternatively mean a seal that passes a coating visualinspection, an adhesion test, a chemical resistance test, and/or acoating fatigue test, device fatigue in an in vitro test, device fatiguein a simulated in vivo environment test, a resistance test in asimulated in vivo environment Examples of such tests include, but arenot limited to, ASTM D6677, ASTM D3359, ASTM D4541, ASTM D2197, ASTMD2370, ASTM D5179, ASTM D4145, ASTM 4146, ASTM F1854-01.

“Polymer” as used herein, refers to a series of repeating monomericunits that have been cross-linked or polymerized. Any suitable polymercan be used to carry out the present invention. It is possible that thepolymers of the invention may also comprise two, three, four or moredifferent polymers. In some embodiments, of the invention only onepolymer is used. In some preferred embodiments a combination of twopolymers are used. Combinations of polymers can be in varying ratios, toprovide coatings with differing properties. Those of skill in the art ofpolymer chemistry will be familiar with the different properties ofpolymeric compounds. Examples of ploymers that may be used in thepresent invention include, but are not limited to polycarboxylic acids,cellulosic polymers, proteins, polypeptides, polyvinylpyrrolidone,maleic anhydride polymers, polyamides, polyvinyl alcohols, polyethyleneoxides, glycosaminoglycans, polysaccharides, polyesters, polyurethanes,polystyrenes, copolymers, silicones, polyorthoesters, polyanhydrides,copolymers of vinyl monomers, polycarbonates, polyethylenes,polypropylenes, polylactic acids, polyglycolic acids, polycaprolactones,polyhydroxybutyrate valerates, polyacrylamides, polyethers, polyurethanedispersions, polyacrylates, acrylic latex dispersions, polyacrylic acid,mixtures and copolymers thereof. The polymers of the present inventionmay be natural or synthetic in origin, including gelatin, chitosan,dextrin, cyclodextrin, Poly(urethanes), Poly(siloxanes) or silicones,Poly(acrylates) such as poly(methyl methacrylate), poly(butylmethacrylate), and Poly(2-hydroxy ethyl methacrylate), Poly(vinylalcohol) Poly(olefins) such as poly(ethylene), poly(isoprene),halogenated polymers such as Poly(tetrafluoroethylene)—and derivativesand copolymers such as those commonly sold as Teflon® products,Poly(vinylidine fluoride), Poly(vinyl acetate), Poly(vinyl pyrrolidone),Poly(acrylic acid), Polyacrylamide, Poly(ethylene-co-vinyl acetate),Poly(ethylene glycol), Poly(propylene glycol), Poly(methacrylic acid);etc. Suitable polymers also include absorbable and/or resorbablepolymers including the following, combinations, copolymers andderivatives of the following: Polylactides (PLA), Polyglycolides (PGA),Poly(lactide-co-glycolides) (PLGA), Polyanhydrides, Polyorthoesters,Poly(N-(2-hydroxypropyl) methacrylamide), Poly(1-aspartamide), etc.

“Water-vapor trapping material” as used herein includes, but is notlimited to a hydrophilic polymer. “Water-vapor trapping material” asused herein includes, but is not limited to a highly absorbent material,which may comprises a superabsorbent polymer. Examples of water-vaportrapping materials include, but are not limited to, acrylate polymers,generally formed from acrylic acid, methacrylic acid, acrylate, methylacrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, adialkylaminoalkyl acrylate, a dialkylaminoalkyl methacrylate, atrialkylammonioalkyl acrylate, and/or a trialkylammonioalkylmethacrylate, and include the polymers or copolymers of acrylic acid,methacrylic acid, methyl methacrylate, ethyl methacrylate,2-dimethylaminoethyl methacrylate, and trimethylammonioethylmethacrylate chloride. Examples of hydrophilic polymers include, but isnot limited to poly(N-vinyl lactams), poly(N-vinyl acrylamides),poly(N-alkylacrylamides), substituted and unsubstituted acrylic andmethacrylic acid polymers, polyvinyl alcohol (PVA), polyvinylamine,copolymers thereof and copolymers with other types of hydrophilicmonomers (e.g. vinyl acetate), polysaccharides, crosslinked acrylatepolymers and copolymers, carbomers, crosslinked acrylamide-sodiumacrylate copolymers, gelatin, vegetable polysaccharides, such asalginates, pectins, carrageenans, or xanthan, starch and starchderivatives, galactomannan and galactomannan derivatives. polyvinylpyrrolidone (PVP), poly(N-vinyl caprolactam) (PVCap), poly(N-vinylacetamides), polyacrylic acid, polymethacrylic acid, and copolymers andblends thereof. PVP and PVCap. Examples of superabsorbent polymersinclude hydrogels. Copolymers of any of the water-vapor trappingmaterials mentioned herein, and blends thereof may also be used.

“Hydrophobic polymer” as used herein can refer to any polymer resistantto wetting, or not readily wet, by water, i.e., having a lack ofaffinity for water. Examples of hydrophobic polymers include, by way ofillustration only, polyolefins, such as polyethylene, poly(isobutene),poly(isoprene), poly(4-methyl-1-pentene), polypropylene,ethylene-propylene copolymers, ethylene-propylene-hexadiene copolymers,and ethylene-vinyl acetate copolymers; metallocene polyolefins, such asethylene-butene copolymers and ethylene-octene copolymers; styrenepolymers, such as poly(styrene), poly(2-methylstyrene), andstyrene-acrylonitrile copolymers having less than about 20 mole-percentacrylonitrile; vinyl polymers, such as poly(vinyl butyrate), poly(vinyldecanoate), poly(vinyl dodecanoate), poly(vinyl hexadecanoate),poly(vinyl hexanoate), poly(vinyl octanoate), andpoly(methacrylonitrile); acrylic polymers, such as poly(n-butylacetate), and poly(ethyl acrylate); methacrylic polymers, such aspoly(benzyl methacrylate), poly(n-butyl methacrylate), poly(isobutylmethacrylate), poly(t-butyl methacrylate), poly(t-butylaminoethylmethacrylate), poly(do-decyl methacrylate), poly(ethyl methacrylate),poly(2-ethylhexyl methacrylate), poly(n-hexyl methacrylate), poly(phenylmethacrylate), poly(n-propyl methacrylate), and poly(octadecylmethacrylate); polyesters, such a poly(ethylene terephthalate) andpoly(butylene terephthalate); and polyalkenes and polyalkynes, such aspolybutylene and polyacetylene. Copolymers of any of the hydrophobicpolymers mentioned herein, and blends thereof may also be used. Thehydrophobic polymer also may contain minor amounts of additives as iscustomary in the art. For example, the hydrophobic polymer may containpigments, delustrants, antioxidants, antistatic agents, stabilizers,oxygen scavengers, and the like. In some embodiments, the hydrophobicpolymer is a polymer having a bulk density of at least about 1.00 gramsper cubic centimeter (g/cc). In some embodiments, the hydrophobicpolymer is a polymer having a bulk density of greater than about 1.00gram per cubic centimeter (g/cc). In some embodiments, the hydrophobicpolymer is a polymer having a bulk density of one of at least about1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03,2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15,2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27,2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39,2.40 grams per cubic centimeter (g/cc). In referring to bulk density,“about” refers to variations of 0.001 to 0.005, or of 0.005 to 0.01grams per cubic centimeter (g/cc).

“Polyolefin” as used herein can refer to a polymer prepared by theaddition polymerization of one or more unsaturated monomers whichcontain only carbon and hydrogen atoms. Examples of such polyolefinsinclude polyethylene, polypropylene, poly(1-butene), poly(2-butene),poly(1-pentene), poly(2-pentene), poly(3-methyl-1-pentene),poly(4-methyl-1-pentene), and the like. In addition, such term is meantto include blends of two or more polyolefins and random and blockcopolymers prepared from two or more different unsaturated monomers.

“Compressed fluid” as used herein refers to a fluid of appreciabledensity (e.g., >0.2 g/cc) that is a gas at standard temperature andpressure. “Supercritical fluid”, “near-critical fluid”,“near-supercritical fluid”, “critical fluid”, “densified fluid” or“densified gas” as used herein refers to a compressed fluid underconditions wherein the temperature is at least 80% of the criticaltemperature of the fluid and the pressure is at least 50% of thecritical pressure of the fluid.

Examples of substances that demonstrate supercritical or near criticalbehavior suitable for the present invention include, but are not limitedto carbon dioxide, isobutylene, ammonia, water, methanol, ethanol,ethane, propane, butane, pentane, dimethyl ether, xenon, sulfurhexafluoride, halogenated and partially halogenated materials such aschlorofluorocarbons, hydrochlorofluorocarbons, hydrofluorocarbons,perfluorocarbons (such as perfluoromethane and perfluoropropane,chloroform, trichloro-fluoromethane, dichloro-difluoromethane,dichloro-tetrafluoroethane), 1,1,1,2,3,3-hexafluoropropane (R236ea) andmixtures thereof.

“Sintering” as used herein refers to the process by which theco-deposited impermeable dispersed solid-polymer matrix, as describedherein, or the hydrophobic polymer and water-vapor-trapping materialbecomes fused and adherent to the substrate by treatment of the coatedsubstrate with a compressed gas, compressed liquid, or supercriticalfluid that is a non-solvent for both the polymer and the impermeabledispersed solid or the hydrophobic polymer and water-vapor-trappingmaterial, but a plasticizing agent for the polymer(s).

“Rapid Expansion of Supercritical Solutions” or “RESS” as used hereininvolves the dissolution of a polymer into a compressed fluid, typicallysupercritical CO₂, followed by rapid expansion into a chamber atatmospheric pressure. The rapid expansion of the supercritical fluidsolution through a small opening, with its accompanying decrease indensity, reduces the dissolution capacity of the fluid and results inthe nucleation and growth of polymer particles.

“Solution Enhanced Dispersion of Supercritical Solutions” or “SEDS” asused herein involves a spray process for the generation of polymerparticles, which are formed when a compressed fluid (e.g. supercriticalfluid, preferably supercritical CO₂) is used as a diluent to a vehiclein which a polymer dissolved, (one that can dissolve both the polymerand the compressed gas). The mixing of the compressed fluid diluent withthe polymer-containing solution may be achieved by encounter of a firststream containing the polymer solution and a second stream containingthe diluent compressed fluid, for example, within one spray nozzle or bythe use of multiple spray nozzles. The solvent in the polymer solutionmay be one compound or a mixture of two or more ingredients and may beor comprise an alcohol (including diols, triols, etc.), ether, amine,ketone, carbonate, or alkanes, or hydrocarbon (aliphatic or aromatic) ormay be a mixture of compounds, such as mixtures of alkanes, or mixturesof one or more alkanes in combination with additional compounds such asone or more alcohols. (e.g., from 0 or 0.1 to 5% of a C₁ to C₁₅ alcohol,including diols, triols, etc.). See for example U.S. Pat. No. 6,669,785.The solvent may optionally contain a surfactant, as also described in(for example) U.S. Pat. No. 6,669,785.

In one embodiment of the SEDS process, a first stream of fluidcomprising a polymer dissolved in a common solvent is co-sprayed with asecond stream of compressed fluid. Polymer particles are produced as thesecond stream acts as a diluent that weakens the solvent in the polymersolution of the first stream. The now combined streams of fluid, alongwith the polymer particles, flow out of the nozzle assembly into acollection vessel. Control of particle size, particle size distribution,and morphology is achieved by tailoring the following process variables:temperature, pressure, solvent composition of the first stream,flow-rate of the first stream, flow-rate of the second stream,composition of the second stream (where soluble additives may be addedto the compressed gas), and conditions of the capture vessel. Typicallythe capture vessel contains a fluid phase that is at least five to tentimes (5-10×) atmospheric pressure.

“Electrostatically charged” or “electrical potential” or “electrostaticcapture” as used herein refers to the collection of the spray-producedparticles upon a substrate that has a different electrostatic potentialthan the sprayed particles. Thus, the substrate is at an attractiveelectronic potential with respect to the particles exiting, whichresults in the capture of the particles upon the substrate. i.e. thesubstrate and particles are oppositely charged, and the particlestransport through the fluid medium of the capture vessel onto thesurface of the substrate is enhanced via electrostatic attraction. Thismay be achieved by charging the particles and grounding the substrate orconversely charging the substrate and grounding the particles, or bysome other process, which would be easily envisaged by one of skill inthe art of electrostatic capture.

“Electrostatic Rapid Expansion of Supercritical Solutions” or “e-RESS”or “eRESS” as used herein refers to Electrostatic Capture as describedherein combined with Rapid Expansion of Supercritical Solutions asdescribed herein.

“Electrostatic Solution Enhanced Dispersion of Supercritical Solutions”or “e-SEDS” or “eSEDS” as used herein refers to Electrostatic Capture asdescribed herein combined with Solution Enhanced Dispersion ofSupercritical Solutions as described herein.

“Electrostatic Dry Powder Coating” or “e-DPC” or “eDPC” as used hereinrefers to Electrostatic Capture as described herein combined with DryPowder Coating. e-DPC deposits material (including, for example, polymeror impermeable dispersed solid) on the device or other substrate as drypowder, using electrostatic capture to attract the powder particles tothe substrate. Dry powder spraying (“Dry Powder Coating” or “DPC”) iswell known in the art, and dry powder spraying coupled withelectrostatic capture has been described, for example in U.S. Pat. Nos.5,470,603; 6,319,541; or 6,372,246.

“Open vessel” as used herein refers to a vessel open to the outsideatmosphere, and thus at substantially the same temperature and pressureas the outside atmosphere.

“Closed vessel” as used herein refers to a vessel sealed from theoutside atmosphere, and thus may be at significantly differenttemperatures and pressures to the outside atmosphere.

EXAMPLES

The following examples are given to enable those skilled in the art tomore clearly understand and to practice the present invention. Theyshould not be considered as limiting the scope of the invention, butmerely as being illustrative and representative thereof.

Example 1

A biocompatible fluoropolymer or other hydrophobic biocompatible polymeris dissolved in an appropriate supercritical solvent such as carbondioxide. This solution is maintained in a syringe pump or other pressurevessel and transferred to a spraying vessel that is maintained above thecompressed gas's critical pressure and temperature as modified by thesolute. The device or other substrate to be coated is held such that itcan placed at an electrical potential relative to a nozzle through whichthe compressed gas solution is to be sprayed (10 kV, for example, withthe device held at 5 kV and the nozzle held at −5 kV). The electricalfield between the device and the nozzle is designed to be homogenous andconstant. The polymer solution is expanded through the restrictor nozzleby electrostatic rapid expansion of a supercritical solution (e-RESS),thereby coating the device with a fine film controllable in boththickness and conformality. Subsequent processing in the gas in itsuncompressed state further reduces the volume of the film increasing itsconformality. A second layer is deposited consisting of a silicon basedpolymer in the same manner as the first polymer layer. Alternatively,this polymer could be deposited as a dry dispersed solid using e-DPC orfrom solution in a compressed gas solvent. This silicon based polymer isselected so that it traps any water vapor that permeates thefluoropolymer layer. Finally, the polymer stack is completed bydeposition of another layer of fluoropolymer using the e-RESS processand processed to reduce its volume (processing in the gas in itsuncompressed state to further reduce the volume of the film and increaseits conformality).

Example 2

A biocompatible fluoropolymer or other hydrophobic biocompatible polymeris dissolved in an appropriate supercritical solvent such as carbondioxide. This solution is maintained in a syringe pump or other pressurevessel and transferred to a spraying vessel that is maintained above thecompressed gas's critical pressure and temperature as modified by thesolute. The device or other substrate to be coated is held such that itcan placed at an electrical potential relative to a nozzle through whichthe compressed gas solution is to be sprayed (10 kV, for example, withthe device held at 5 kV and the nozzle held at −5 kV). The electricalfield between the device and the nozzle is designed to be homogenous andconstant. The polymer solution is expanded through the restrictor nozzleby electrostatic rapid expansion of a supercritical solution (e-RESS),thereby coating the device with a fine film controllable in boththickness and conformality. Subsequent processing in the gas in itsuncompressed state further reduces the volume of the film increasing itsconformality. A second layer of carbonaceous material is deposited bye-DPC. A quantity of carbonaceous material is loaded as a plug into achamber. The quantity of material initially loaded is dependent upon thedesired coating mass and is a function of the potential at which thedevice or other substrate is held and the backpressure placed on theplug. A valve is rapidly opened through which the material expandscreating an aerosolized cloud which coats the device or other substrateas a dry powder. This coating is immediately followed with a secondfluoropolymer coating and undergoes the same volume reducing process asthe initial layer (processing in the gas in its uncompressed state tofurther reduce the volume of the film and increase its conformality).

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following Claims define the scope of the invention and that methodsand structures within the scope of these Claims and their equivalents becovered thereby.

1. A method of preparing a coated substrate comprising: providing asubstrate; depositing on said substrate at least one layer comprising apolymer, wherein the layer substantially seals the substrate.
 2. Themethod of claim 1, wherein the layer is substantially impermeable to agas.
 3. The method of claim 1, wherein the layer is substantiallyimpermeable to a fluid.
 4. The method of claim 1, wherein the layer issubstantially impervious to a biological material.
 5. The method ofclaim 1, wherein the polymer is hydrophobic.
 6. The method of claim 1,wherein the polymer is at least one of a polyolefin, a metallocenepolyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, apolyester, a polyalkene, and a polyalkynes.
 7. The method of claim 1,wherein the polymer has a bulk density of at least about 1.00 grams percubic centimeter (g/cc).
 8. The method of claim 1, wherein the polymerhas a bulk density of greater than about 1.00 gram per cubic centimeter(g/cc).
 9. The method of claim 1, wherein the polymer has a bulk densityof at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09,2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11,2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23,2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35,2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
 10. Themethod of claims 1, further comprising: depositing on said substrate atleast one layer comprising an impermeable dispersed solid.
 11. Themethod of claim 1, wherein the layer provides a substantially conformalcoating on the substrate.
 12. The method of claim 1, wherein the layerprovides a coating that is substantially impermeable to leachants fromthe substrate.
 13. The method of claim 12, wherein the impermeabledispersed solid is impermeable to a gas.
 14. The method of claim 1,wherein the substrate is a medical device.
 15. The method of claim 14,wherein the medical device is an active medical device.
 16. The methodof claim 1, further comprising depositing on said substrate one or morepolymer layers.
 17. The method of one of claim 1, further comprisingdepositing on said substrate one or more impermeable dispersed solidlayers.
 18. The method of claim 1, comprising depositing 5, 10, 20, 50,or 100 layers of at least one of a polymer and an impermeable dispersedsolid.
 19. The method of claim 10, comprising depositing saidimpermeable dispersed solid layer by an e-RESS, an e-SEDS, or an e-DPCprocess.
 20. The method of claim 1, comprising depositing said polymerlayer by an e-RESS, an e-SEDS, or an e-DPC process.
 21. The method ofclaim 1, wherein the polymer layer is substantially defect-free.
 22. Themethod of claim 1, comprising depositing a coating formed by the polymerlayer and an impermeable dispersed solid layer in combination whereinthe coating is substantially defect-free.
 23. The method of claim 10,wherein depositing said impermeable dispersed solid layer providesimproved adherence of the impermeable dispersed solid to at least one ofthe substrate and the polymer layer.
 24. The method of claim 1, whereindepositing said polymer layer provides improved adherence of the polymerto the substrate.
 25. A method of preparing a coated substratecomprising: providing a substrate; depositing on said substrate at leastone layer comprising an impermeable dispersed solid and a polymer. 26.The method of claim 25, wherein the layer substantially seals thesubstrate.
 27. The method of claim 25, wherein the layer issubstantially impermeable to a gas.
 28. The method of claim 25, whereinthe layer is substantially impermeable to a fluid.
 29. The method ofclaim 25, wherein the layer is substantially impervious to a biologicalmaterial.
 30. The method of claim 25, wherein the polymer ishydrophobic.
 31. The method of claim 25, wherein the polymer is at leastone of a polyolefin, a metallocene polyolefins, a styrene polymers, avinyl polymer, an acrylic polymers, a polyester, a polyalkene, and apolyalkynes.
 32. The method of claim 25, wherein the polymer has a bulkdensity of at least about 1.00 grams per cubic centimeter (g/cc). 33.The method of claim 25, wherein the polymer has a bulk density ofgreater than about 1.00 gram per cubic centimeter (g/cc).
 34. The methodof claim 25, wherein the polymer has a bulk density of at least aboutone of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02,2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14,2.15, 2.25, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26,2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38,2.39, 2.40 grams per cubic centimeter (g/cc).
 35. The method of claim25, wherein the layer provides a substantially conformal coating on thesubstrate.
 36. The method of claim 25, wherein the layer provides acoating that is substantially impermeable to leachants from thesubstrate.
 37. The method of claim 25, wherein the impermeable dispersedsolid is impermeable to a gas.
 38. The method of claim 25, wherein thesubstrate is a medical device.
 39. The method of claim 38, wherein themedical device is an active medical device.
 40. The method of claim 25,comprising depositing 5, 10, 20, 50, or 100 layers of at least one of apolymer and a impermeable dispersed solid.
 41. The method of claim 25,comprising depositing said layer by an e-RESS, an e-SEDS, or an e-DPCprocess.
 42. The method of claim 25, wherein the layer is substantiallydefect-free.
 43. The method of claim 25, wherein depositing said layerprovides improved adherence of the layer to the substrate.
 44. A methodfor depositing a coating comprising a polymer on a substrate, comprisingthe following steps: discharging at least one polymer in dry powder formthrough a first orifice; depositing the polymer onto said substrate,wherein an electrical potential is maintained between the substrate andthe polymer particles, thereby forming said coating; and sintering saidcoating under conditions that do not substantially disrupt the activityand/or function of the substrate, wherein the coating substantiallyseals the substrate.
 45. The method of claim 44, further comprising:discharging at least one impermeable dispersed solid in dry powder formthrough a second orifice.
 46. The method of claim 45, furthercomprising: depositing the gas impermeable dispersed solid onto saidsubstrate, wherein an electrical potential is maintained between thesubstrate and the impermeable dispersed solid.
 47. The method of claim45, wherein the impermeable dispersed solid and/or the polymer becomeselectrostatically charged prior to deposition on said substrate.
 48. Themethod of claim 45, wherein the substrate is electrostatically charged.49. The method of claim 45, wherein the substrate is electricallygrounded, and the impermeable dispersed solid and/or the polymerparticles are charged.
 50. The method of claim 45, wherein said polymerand said impermeable dispersed solid are discharged using a gas basedpropellant.
 51. The method of claim 50, wherein said gas basedpropellant comprises at least one of the members selected from the groupconsisting of carbon dioxide, nitrous oxide, hydrofluorocarbons,chlorofluorocarbons, helium, nitrogen, compressed air, argon, andvolatile hydrocarbons with a vapor pressure greater than 750 Torr at 20°C.
 52. The method of claim 51, wherein said gas based propellantcomprises carbon dioxide.
 53. The method of claim 45, wherein theaverage particle size of said polymer and/or impermeable dispersed solidparticles is from about 0.1 micron to about 100 microns.
 54. The methodof claim 45, wherein the molecular weight range of said polymer is fromabout 5,000 a.u. to about 100,000 a.u.
 55. The method of claim 45,wherein the resistivity of said polymer and/or impermeable dispersedsolid dry powders is from about 106 Ωm to about 1024 Ωm.
 56. The methodof claim 45, wherein the moisture content of said polymer and/orimpermeable dispersed solid dry powders is less than 5% by weight. 57.The method of claim 45, wherein said first and said second orifices areprovided as one single orifice.
 58. The method of claim 57, wherein saidimpermeable dispersed solid and said polymer are mixed together prior todischarging.
 59. The method of claim 45, wherein said impermeabledispersed solid and said polymer particles are dischargedsimultaneously.
 60. The method of claim 45, wherein said impermeabledispersed solid and said polymer particles are discharged in succession.61. The method of claim 45, carried out at a temperature from about 0°C. to about 80° C.
 62. The method of one of claims 1, 25, and 44,wherein the impermeable dispersed solid comprises a nanoparticle. 63.The method of claim 62, wherein the nanoparticle is a polyurethaneadhesive nanocomposite.
 64. The method of claim 62, wherein thenanoparticle comprises organically modified montmorillonite andpolyurethane.
 65. The method of one of claims 1, 25, and 44, wherein theoxygen transmission rate across the coating is at most about 1%, 5%,10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 66. The method of one of claims 1,25, and 44, wherein the water vapor permeation through the coating is atmost about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 67. The methodof one of claims 1, 25, and 44, wherein the small particle transmissionrate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%,10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 68. The method of claim 44,carried out at a pressure from about 0.1 atmospheres to about 73atmospheres.
 69. The method of claim 44, wherein said substrate is abiomedical implant.
 70. The method of claim 69, wherein said biomedicalimplant is selected from the group consisting of a stent (e.g., vascularstents), electrode, catheter, lead, implantable pacemaker, implantablecardioverter, a housing for an implantable pacemaker, a housing for animplantable defibrillator, a housing for an implantable cardioverter,sensor, drug delivery device, therapy delivery device, device comprisingtelemetry capability, device comprising electrical impulses, diagnosticdevice, measurement device, joint, screw, rod, ophthalmic implant,femoral pin, bone plate, graft, anastomotic device, perivascular wrap,suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bagattachment device, ear drainage tube, lead for pace makers andimplantable cardioverters and defibrillators, vertebral disk, bone pin,suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascularimplant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmicimplant, prosthetic, shunt, urologic implant, reproductive anatomydevice, gastrologic device, neurologic lead, neurologic device, varioustypes of dressings (e.g., wound dressings), bone substitutes,intraluminal devices, and vascular supports.
 71. The method of claim 44,wherein said sintering comprises treating said coated substrate with acompressed gas, compressed liquid, or supercritical fluid that is anon-solvent for both the polymer and the impermeable dispersed solid,but a plasticizing agent for the polymer.
 72. The method of claim 71,wherein said compressed gas, compressed liquid, or supercritical fluidis carbon dioxide.
 73. The method of any of claims 1, 25, and 44,wherein at least one of the polymer and the impermeable dispersed solidis electrostatically deposited onto the substrate, wherein the polymerinitially forms a coating of individual polymer nanoparticles thatsubsequently coalesce with adjacent polymer nanoparticles to form apolymer film.
 74. The method of claim 73, wherein the polymer filmcomprises a microstructure.
 75. The method of claim 74, wherein theimpermeable dispersed solid is are sequestered within saidmicrostructure.
 76. The method of claim 44, wherein the coating issubstantially impermeable to a gas.
 77. The method of claim 44, whereinthe coating is substantially impermeable to a fluid.
 78. The method ofclaim 44, wherein the coating is substantially impervious to abiological material.
 79. The method of claim 44, wherein the polymer ishydrophobic.
 80. The method of claim 44, wherein the polymer is at leastone of a polyolefin, a metallocene polyolefins, a styrene polymers, avinyl polymer, an acrylic polymers, a polyester, a polyalkene, and apolyalkyne.
 81. The method of claim 44, wherein the polymer has a bulkdensity of at least about 1.00 grams per cubic centimeter (g/cc). 82.The method of claim 44, wherein the polymer has a bulk density ofgreater than about 1.00 gram per cubic centimeter (g/cc).
 83. The methodof claim 44, wherein the polymer has a bulk density of at least aboutone of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02,2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14,2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26,2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38,2.39, 2.40 grams per cubic centimeter (g/cc).
 84. A substrate comprisinga coating deposited on said substrate according to any of claims 1-83.85. A device comprising: a substrate and a polymer layer disposed on thesubstrate wherein the layer substantially seals the substrate.
 86. Thedevice of claim 85, wherein said substrate is a medical device.
 87. Thedevice of claim 86, wherein said medical device is selected from a stent(e.g., vascular stents), electrode, catheter, lead, implantablepacemaker, implantable cardioverter, a housing for an implantablepacemaker, a housing for an implantable defibrillator, a housing for animplantable cardioverter, sensor, drug delivery device, therapy deliverydevice, device comprising telemetry capability, device comprisingelectrical impulses, diagnostic device, measurement device, joint,screw, rod, ophthalmic implant, femoral pin, bone plate, graft,anastomotic device, perivascular wrap, suture, staple, shuntsforhydrocephalus, dialysis graft, colostomy bag attachment device, eardrainage tube, lead for pace makers and implantable cardioverters anddefibrillators, vertebral disk, bone pin, suture anchor, hemostaticbarrier, clamp, screws, plate, clip, vascular implant, tissue adhesive,sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt,urologic implant, reproductive anatomy device, gastrologic device,neurologic lead, neurologic device, various types of dressings (e.g.,wound dressings), bone substitutes, intraluminal devices, and vascularsupports.
 88. The device of claim 85, wherein the polymer layer issubstantially impermeable to a gas.
 89. The device of claim 85, whereinthe polymer layer is substantially impermeable to a fluid.
 90. Thedevice of claim 85, wherein the polymer layer is substantiallyimpervious to a biological material.
 91. The device of claim 85, whereinthe polymer layer is hydrophobic.
 92. The device of claim 85, whereinthe polymer layer comprises at least one of a polyolefin, a metallocenepolyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, apolyester, a polyalkene, and a polyalkyne.
 93. The device of claim 85,wherein a polymer in the polymer layer has a bulk density of at leastabout 1.00 grams per cubic centimeter (g/cc).
 94. The device of claim85, wherein a polymer in the polymer layer has a bulk density of greaterthan about 1.00 gram per cubic centimeter (g/cc).
 95. The device ofclaim 85, wherein a polymer in the polymer layer has a bulk density ofat least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09,2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11,2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23,2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35,2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
 96. Thedevice of claim 85, wherein the polymer layer provides a substantiallyconformal coating on the substrate.
 97. The method of claims 85, whereinthe polymer layer provides a coating that is substantially impermeableto leachants from the substrate.
 98. The device of claim 85, comprising:at least one layer comprising an impermeable dispersed solid.
 99. Thedevice of claim 98, wherein the polymer layer and the impermeabledispersed solid layer in combination provide a substantially conformalcoating on the substrate.
 100. The device of claims 98, wherein thepolymer layer and the impermeable dispersed solid layer in combinationprovide a coating that is substantially impermeable to leachants fromthe substrate.
 101. The device of claim 98, wherein the impermeabledispersed solid is impermeable to a gas.
 102. The device of claim 98,comprising 5, 10, 20, 50, or 100 layers of at least one of a polymer andan impermeable dispersed solid.
 103. The device of claim 98, wherein thepolymer layer is substantially defect-free.
 104. The device of claim 98,wherein a coating formed by the polymer layer and the impermeabledispersed solid layer in combination is substantially defect-free. 105.A device comprising: a substrate and a layer disposed on the substrate,said layer comprising a polymer and an impermeable dispersed solidwherein the layer substantially seals the substrate.
 106. The device ofclaim 105, wherein said substrate is a medical device.
 107. The deviceof claim 105, wherein said medical device is selected from a stent(e.g., vascular stents), electrode, catheter, lead, implantablepacemaker, implantable cardioverter, a housing for an implantablepacemaker, a housing for an implantable defibrillator, a housing for animplantable cardioverter, sensor, drug delivery device, therapy deliverydevice, device comprising telemetry capability, device comprisingelectrical impulses, diagnostic device, measurement device, joint,screw, rod, ophthalmic implant, femoral pin, bone plate, graft,anastomotic device, perivascular wrap, suture, staple, shuntsforhydrocephalus, dialysis graft, colostomy bag attachment device, eardrainage tube, lead for pace makers and implantable cardioverters anddefibrillators, vertebral disk, bone pin, suture anchor, hemostaticbarrier, clamp, screws, plate, clip, vascular implant, tissue adhesive,sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt,urologic implant, reproductive anatomy device, gastrologic device,neurologic lead, neurologic device, various types of dressings (e.g.,wound dressings), bone substitutes, intraluminal devices, and vascularsupports.
 108. The device of claim 105, wherein the layer issubstantially impermeable to a gas.
 109. The device of claim 105,wherein the layer is substantially impermeable to a fluid.
 110. Thedevice of claim 105, wherein the layer is substantially impervious to abiological material.
 111. The device of claim 105, wherein the layer ishydrophobic.
 112. The device of claim 105, wherein the polymer comprisesat least one of a polyolefin, a metallocene polyolefins, a styrenepolymers, a vinyl polymer, an acrylic polymers, a polyester, apolyalkene, and a polyalkyne.
 113. The device of claim 105, wherein apolymer has a bulk density of at least about 1.00 grams per cubiccentimeter (g/cc).
 114. The device of claim 105, wherein a polymer has abulk density of greater than about 1.00 gram per cubic centimeter(g/cc).
 115. The device of claim 105, wherein a polymer has a bulkdensity of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07,1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09,2.10, 2.11, 2.12, 2.13, 2.14, 115, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21,2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33,2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter(g/cc).
 116. The device of claim 105, wherein the layer provides asubstantially conformal coating on the substrate.
 117. The method ofclaim 105, wherein the layer provides a coating that is substantiallyimpermeable to leachants from the substrate.
 118. The device of claim105, wherein the impermeable dispersed solid is impermeable to a gas.119. The device of claim 105, comprising 5, 10, 20, 50, or 100 layers ofat least one of the polymer and the impermeable dispersed solid. 120.The device of claim 105, wherein the layer is substantially defect-free.121. A method of preparing a coated substrate comprising: providing asubstrate; depositing on said substrate at least one layer comprising awater-vapor-trapping material, and depositing on said substrate at leastone layer comprising a hydrophobic polymer.
 122. The method of claim121, wherein the hydrophobic polymer layer and the water-vapor-trappingmaterial substantially seals the substrate.
 123. The method of claim121, wherein the hydrophobic polymer comprises a fluoropolymer.
 124. Themethod of claim 121, wherein the water-vapor-trapping material comprisesa silicon based polymer.
 125. The method of claim 124, wherein thesilicon based polymer comprises native silicon and is metallized withtitanium.
 126. The method of claim 121, comprising depositing at least athird layer of a hydrophobic polymer encapsulate thewater-vapor-trapping material between the hydrophobic polymer layers.127. The method of claim 126, wherein the hydrophobic polymer comprisesa fluoropolymer.
 128. The method of claim 126, wherein thewater-vapor-trapping material comprises a silicon based polymer. 129.The method of claim 128, wherein the silicon based polymer comprisesnative silicon and is metallized with titanium.
 130. The method of claim121, comprising depositing multiple alternating layers of a hydrophobicpolymer and a water-vapor-trapping material.
 131. The method of claim121, wherein the water-vapor-trapping material comprises a hydrophilicpolymer.
 132. The method of claim 121, wherein the hydrophobic polymeris at least one of a polyolefin, a metallocene polyolefins, a styrenepolymers, a vinyl polymer, an acrylic polymers, a polyester, apolyalkene, and a polyalkyne.
 133. The method of claim 121, wherein thehydrophobic polymer has a bulk density of at least about 1.00 grams percubic centimeter (g/cc).
 134. The method of claim 121, wherein thehydrophobic polymer has a bulk density of greater than about 1.00 gramper cubic centimeter (g/cc).
 135. The method of claim 121, wherein thehydrophobic polymer has a bulk density of at least about one of 1.01,1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04,2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16,2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28,2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40grams per cubic centimeter (g/cc).
 136. The method of claim 121, whereinthe water-vapor-trapping material comprises a superabsorbent polymer.137. The method of claim 121, wherein the hydrophobic polymer layer andthe water-vapor-trapping later in combination provide a substantiallyconformal coating on the substrate.
 138. The method of claim 121,wherein the coated substrate is impervious to a biological material.139. The method of claim 121, wherein the hydrophobic polymer layer andthe water-vapor-trapping later in combination provide a coating that issubstantially impermeable to leachants from the substrate.
 140. Themethod of claim 121, wherein the impermeable dispersed solid isimpermeable to a gas.
 141. The method of claim 121, wherein thesubstrate is a medical device.
 142. The method of claim 141, wherein themedical device is an active medical device.
 143. The method of claim121, further comprising depositing one or more water-vapor-trappingmaterial layers.
 144. The method of claim 121, further comprisingdepositing one or more hydrophobic polymer layers.
 145. The method ofclaim 121, comprising depositing 5, 10, 20, 50, or 100 layers of atleast one of a water-vapor-trapping material and a hydrophobic polymer.146. The method of claim 121, comprising depositing said hydrophobicpolymer layer by an e-RESS, an e-SEDS, or an e-DPC process.
 147. Themethod of claim 121, comprising depositing said water-vapor-trappingmaterial layer by an e-RESS, an e-SEDS, or an e-DPC process.
 148. Themethod of claim 121, wherein at least one of the hydrophobic polymer andthe water-vapor-trapping material comprises a nanoparticle.
 149. Themethod of claim 121, wherein the nanoparticle is a polyurethane adhesivenanocomposite.
 150. The method of claim 149, wherein the nanoparticlecomprises organically modified montmorillonite and polyurethane. 151.The method of claim 121, wherein the oxygen transmission rate across thecoating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.152. The method of claim 121, wherein the water vapor permeation throughthe coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or70%.
 153. The method of claim 121, wherein the small particletransmission rate across the coating is at most about 0.001%, 0.01%,0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 154. The method ofclaim 121, wherein the hydrophobic polymer layer and thewater-vapor-trapping material layer is substantially defect-free. 155.The method of claim 121, wherein depositing said hydrophobic polymerlayer provides improved adherence of the impermeable dispersed solid tothe substrate.
 156. The method of claim 121, comprising depositing saidwater-vapor-trapping material layer provides improved adherence of thewater-vapor-trapping material to at least one of the substrate and thehydrophobic polymer.
 157. A method of preparing a coated substratecomprising: providing a substrate; depositing on said substrate at leastone layer comprising a hydrophobic polymer and a water-vapor-trappingmaterial.
 158. The method of claim 157, wherein the layer substantiallyseals the substrate.
 159. The method of claim 157, wherein the layer issubstantially impermeable to a gas.
 160. The method of claim 157,wherein the layer is substantially impermeable to a fluid.
 161. Themethod of claim 157, wherein the layer is substantially impervious to abiological material.
 162. The method of claim 157, wherein thehydrophobic polymer comprises a fluoropolymer.
 163. The method of claim157, wherein the water-vapor-trapping material comprises a silicon basedpolymer.
 164. The method of claim 163, wherein the silicon based polymercomprises native silicon and is metallized with titanium.
 165. Themethod of claim 157, comprising depositing at least a third layer of ahydrophobic polymer encapsulate the water-vapor-trapping materialbetween the hydrophobic polymer layers.
 166. The method of claim 157,comprising depositing multiple alternating layers of a hydrophobicpolymer and a water-vapor-trapping material.
 167. The method of claim157, wherein the layer provides a substantially conformal coating on thesubstrate.
 168. The method of claim 157, wherein the layer provides acoating that is substantially impermeable to leachants from thesubstrate.
 169. The method of claim 157, wherein the substrate is amedical device.
 170. The method of claim 169, wherein the medical deviceis an active medical device.
 171. The method of claim 157, furthercomprising depositing one or more water-vapor-trapping material layers.172. The method of claim 157, further comprising depositing one or morehydrophobic polymer layers.
 173. The method of claim 157, comprisingdepositing 5, 10, 20, 50, or 100 layers of at least one of awater-vapor-trapping material and a hydrophobic polymer.
 174. The methodof claim 157, comprising depositing said layer by an e-RESS, an e-SEDS,or an e-DPC process.
 175. The method of claim 157, wherein at least oneof the hydrophobic polymer and the water-vapor-trapping materialcomprises a nanoparticle.
 176. The method of claim 175, wherein thenanoparticle is a polyurethane adhesive nanocomposite.
 177. The methodof claim 175, wherein the nanoparticle comprises organically modifiedmontinorillonite and polyurethane.
 178. The method of claim 157, whereinthe oxygen transmission rate across the coating is at most about 1%, 5%,10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 179. The method of claim 157,wherein the water vapor permeation through the coating is at most about1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 180. The method of claim157, wherein the small particle transmission rate across the coating isat most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%,or 70%.
 181. The method of claim 157, wherein the layer is substantiallydefect-free.
 182. A method for depositing a coating comprising awater-vapor-trapping material and hydrophobic polymer on a substrate,comprising the following steps: discharging at least onewater-vapor-trapping material in dry powder form through a secondorifice; discharging at least one hydrophobic polymer in dry powder formthrough a first orifice; depositing the water-vapor-trapping materialand/or hydrophobic polymer onto said substrate, wherein an electricalpotential is maintained between the substrate and the hydrophobicpolymer and/or water-vapor-trapping material particles, thereby formingsaid coating; and sintering said coating under conditions that do notsubstantially disrupt the activity and/or function of the substrate.183. The method of claim 182, wherein the hydrophobic polymer and/or thewater-vapor-trapping material becomes electrostatically charged prior todeposition on said substrate.
 184. The method of claim 182, wherein thesubstrate is electrostatically charged.
 185. The method of claim 182,wherein the substrate is electrically grounded, and the hydrophobicpolymer and/or the water-vapor-trapping material particles are charged.186. The method of claim 182, wherein said water-vapor-trapping materialand said hydrophobic polymer are discharged using a gas basedpropellant.
 187. The method of claim 186, wherein said gas basedpropellant comprises at least one of the members selected from the groupconsisting of carbon dioxide, nitrous oxide, hydrofluorocarbons,chlorofluorocarbons, helium, nitrogen, compressed air, argon, andvolatile hydrocarbons with a vapor pressure greater than 750 Torr at 20°C.
 188. The method of claim 186, wherein said gas based propellantcomprises carbon dioxide.
 189. The method of claim 182, wherein theaverage particle size of said water-vapor-trapping material and/orhydrophobic polymer particles is from about 0.1 micron to about 100microns.
 190. The method of claim 182, wherein the molecular weightrange of said water-vapor-trapping material is from about 5,000 a.u. toabout 100,000 a.u.
 191. The method of claim 182, wherein the resistivityof said water-vapor-trapping material and/or hydrophobic polymer drypowders is from about 106 Ωm to about 1024 Ωm.
 192. The method of claim182, wherein the moisture content of said water-vapor-trapping materialand/or hydrophobic polymer dry powders is less than 5% by weight. 193.The method of claim 188, wherein said first and said second orifices areprovided as one single orifice.
 194. The method of claim 182, whereinsaid hydrophobic polymer and said water-vapor-trapping material aremixed together prior to discharging.
 195. The method of claim 182,wherein said hydrophobic polymer and said water-vapor-trapping materialparticles are discharged simultaneously.
 196. The method of claim 182,wherein said hydrophobic polymer and said water-vapor-trapping materialparticles are discharged in succession.
 197. The method of claim 182,carried out at a temperature from about 0° C. to about 80° C.
 198. Themethod of claim 182, carried out at a pressure from about 0.1atmospheres to about 82 atmospheres.
 199. The method of claim 182,wherein said substrate is a biomedical implant.
 200. The method of claim199, wherein said biomedical implant is selected from the groupconsisting of a stent (e.g., vascular stents), electrode, catheter,lead, implantable pacemaker, implantable cardioverter, a housing for animplantable pacemaker, a housing for an implantable defibrillator, ahousing for an implantable cardioverter, sensor, drug delivery device,therapy delivery device, device comprising telemetry capability, devicecomprising electrical impulses, diagnostic device, measurement device,joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft,anastomotic device, perivascular wrap, suture, staple, shuntsforhydrocephalus, dialysis graft, colostomy bag attachment device, eardrainage tube, lead for pace makers and implantable cardioverters anddefibrillators, vertebral disk, bone pin, suture anchor, hemostaticbarrier, clamp, screws, plate, clip, vascular implant, tissue adhesive,sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt,urologic implant, reproductive anatomy device, gastrologic device,neurologic lead, neurologic device, various types of dressings (e.g.,wound dressings), bone substitutes, intraluminal devices, and vascularsupports.
 201. The method of claim 178, wherein said sintering comprisestreating said coated substrate with a compressed gas, compressed liquid,or supercritical fluid that is a non-solvent for both thewater-vapor-trapping material and the hydrophobic polymer, but aplasticizing agent for the water-vapor-trapping material.
 202. Themethod of claim 201, wherein said compressed gas, compressed liquid, orsupercritical fluid is carbon dioxide.
 203. The method of claim 178,wherein at least one of the hydrophobic polymer and thewater-vapor-trapping material comprises a nanoparticle.
 204. The methodof claim 178, wherein the nanoparticle is a polyurethane adhesivenanocomposite.
 205. The method of claim 204, wherein the nanoparticlecomprises organically modified montmorillonite and polyurethane. 206.The method of claim 178, wherein the oxygen transmission rate across thecoating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.207. The method of claim 178, wherein the water vapor permeation throughthe coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or70%.
 208. The method of claim 178, wherein the hydrophobic polymercomprises a fluoropolymer.
 209. The method of claim 178, wherein thewater-vapor-trapping material comprises a silicon based polymer. 210.The method of claim 178, comprising depositing at least a third layer ofa hydrophobic polymer encapsulate the water-vapor-trapping materialbetween the hydrophobic polymer layers.
 211. The method of claim 178,comprising depositing multiple alternating layers of a hydrophobicpolymer and a water-vapor-trapping material.
 212. The method of claim178, wherein the water-vapor-trapping material comprises a hydrophilicpolymer.
 213. The method of claim 178 wherein the polymer ishydrophobic.
 214. A substrate comprising a coating deposited on saidsubstrate according to any of claims 121-213.
 215. A device comprising:a substrate and a water-vapor-trapping material layer, and a hydrophobicpolymer layer, wherein the water-vapor-trapping material layer isdisposed on the substrate, wherein the hydrophobic layer is disposed onthe water-vapor-trapping material layer, and wherein at least one of thewater-vapor-trapping material layer and the hydrophobic polymer layersubstantially seals the substrate.
 216. The device of claim 215, whereinsaid substrate is an implantable device.
 217. The device of claim 216,wherein said implantable device is selected from a stent (e.g., vascularstents), electrode, catheter, lead, implantable pacemaker, implantablecardioverter, a housing for an implantable pacemaker, a housing for animplantable defibrillator, a housing for an implantable cardioverter,sensor, drug delivery device, therapy delivery device, device comprisingtelemetry capability, device comprising electrical impulses, diagnosticdevice, measurement device, joint, screw, rod, ophthalmic implant,femoral pin, bone plate, graft, anastomotic device, perivascular wrap,suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bagattachment device, ear drainage tube, lead for pace makers andimplantable cardioverters and defibrillators, vertebral disk, bone pin,suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascularimplant, tissue adhesive, sealant, tissue scaffolds, shunts, opthahnicimplant, prosthetic, shunt, urologic implant, reproductive anatomydevice, gastrologic device, neurologic lead, neurologic device, varioustypes of dressings (e.g., wound dressings), bone substitutes,intraluminal devices, and vascular supports.
 218. A device comprising: asubstrate and a layer disposed on the substrate, said layer comprising apolymer and an impermeable dispersed solid wherein the layersubstantially seals the substrate.
 219. The device of claim 218, whereinsaid substrate is a medical device.
 220. The device of claim 218,wherein the layer provides a substantially conformal coating on thesubstrate.
 221. The device of claim 218, wherein the layer issubstantially defect-free.
 222. A method of preparing a coated substratecomprising: providing a substrate; depositing on said substrate at leastone layer comprising a nanoparticle; and depositing on said substrate atleast one layer comprising a polymer, wherein the depositing of thenanoparticle and the polymer in combination substantially seals thesubstrate
 223. The method of claim 222, wherein the substrate is amedical device.
 224. The method of claim 222, further comprisingdepositing one or more polymer layers.
 225. The method of claim 222,further comprising depositing one or more layers of nanoparticles. 226.The method of claim 222, comprising depositing 5, 10, 20, 50, or 100layers of at least one of a polymer and a nanoparticle.
 227. The methodof claim 222, comprising depositing said nanoparticle layer by ane-RESS, an e-SEDS, or an e-DPC process.
 228. The method of claim 222,comprising depositing said polymer layer by an e-RESS, an e-SEDS, or ane-DPC process.
 229. The method of claim 222, comprising depositing saidpolymer layer in a substantially defect-free manner.
 230. A method ofpreparing a conformally coated substrate impervious to a biologicalmaterial comprising: providing a substrate; depositing on said substrateat least one layer comprising a nanoparticle and a polymer whereindepositing the layer substantially seals the substrate
 231. The methodof claim 230, wherein the substrate is a medical device.
 232. The methodof claim 230, comprising depositing said layer by an e-RESS, an e-SEDS,or an e-DPC process.
 233. The method of claim 230, comprising depositingsaid layer in a substantially defect-free manner.
 234. A method fordepositing a coating comprising a polymer and a nanoparticle imperviousto small particle transport on a substrate, comprising the followingsteps: discharging at least one nanoparticle in dry powder form througha first orifice; discharging at least one polymer in dry powder formthrough a second orifice; depositing the polymer and/or nanoparticleonto said substrate, wherein an electrical potential is maintainedbetween the substrate and the nanoparticle and/or polymer particles,thereby forming said coating; and sintering said coating underconditions that do not substantially disrupt the activity and/orfunction of the substrate.
 235. The method of claim 230, wherein thenanoparticle and/or the polymer becomes electrostatically charged priorto deposition on said substrate.
 236. The method of claim 230, whereinthe substrate is electrostatically charged.
 237. The method of claim230, wherein the substrate is electrically grounded, and thenanoparticle and/or the polymer particles are charged.
 238. The methodof claim 230, wherein said polymer and said nanoparticle are dischargedusing a gas based propellant.
 239. The method of claim 230, wherein theaverage particle size of said polymer particle and/or nanoparticle isfrom about 0.1 micron to about 100 microns.
 240. The method of claim230, wherein the molecular weight range of said polymer is from about5,000 a.u. to about 100,000 a.u.
 241. The method of claim 230, whereinthe resistivity of said polymer and/or nanoparticle dry powders is fromabout 106 Ωm to about 1024 Ωm.
 242. The method of claim 230, wherein themoisture content of said polymer and/or nanoparticle dry powders is lessthan 5% by weight.
 243. The method of claim 230, wherein said first andsaid second orifices are provided as one single orifice.
 244. The methodof claim 239, wherein said nanoparticle and said polymer are mixedtogether prior to discharging.
 245. The method of claim 230, whereinsaid nanoparticle and said polymer particles are dischargedsimultaneously.
 246. The method of claim 230, wherein said nanoparticleand said polymer particles are discharged in succession.
 247. The methodof claim 230, carried out at a temperature from about 0° C. to about 80°C.
 248. The method of claim 343, wherein the nanoparticle is apolyurethane adhesive nanocomposite.
 249. The method of claim 345,wherein the nanoparticle comprises organically modified montmorilloniteand polyurethane.
 250. The method of one of claims 222, 230, and 234,wherein the oxygen transmission rate across the coating is at most about1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 251. The method of one ofclaims 222, 230, and 234, wherein the water vapor permeation through thecoating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.252. The method of one of claims 222, 230, and 234, wherein the smallparticle transmission rate across the coating is at most about 0.001%,0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
 253. Themethod of claim 230, carried out at a pressure from about 0.1atmospheres to about 73 atmospheres.
 254. The method of claim 230,wherein said substrate is a biomedical implant.
 255. The method of claim230, wherein said sintering comprises treating said coated substratewith a compressed gas, compressed liquid, or supercritical fluid that isa non-solvent for both the polymer and the impermeable dispersed solid,but a plasticizing agent for the polymer.
 256. The method of claim 230,wherein said compressed gas, compressed liquid, or supercritical fluidis carbon dioxide.
 257. The method of any of claims 222, 230, and 234,wherein at least one of the polymer and the nanoparticle iselectrostatically deposited onto the substrate, wherein the polymerinitially forms a coating of individual polymer nanoparticles thatsubsequently coalesce with adjacent polymer nanoparticles to form apolymer film.
 258. The method of claim 257, wherein the polymer filmcomprises a microstructure.
 259. The method of claim 257, wherein theimpermeable dispersed solid is are sequestered within saidmicrostructure.
 260. A substrate comprising a coating deposited on saidsubstrate according to any of claims 222-259.
 261. A device comprising:a substrate a layer comprising at least one of a nanoparticle and apolymer disposed on the substrate, wherein the layer substantially sealsthe substrate.
 262. The device of claim 261, wherein said substrate is amedical device.
 263. The device of claim 262, wherein said medicaldevice is selected from a stent (e.g., vascular stents), electrode,catheter, lead, implantable pacemaker, implantable cardioverter, ahousing for an implantable pacemaker, a housing for an implantabledefibrillator, a housing for an implantable cardioverter, sensor, drugdelivery device, therapy delivery device, device comprising telemetrycapability, device comprising electrical impulses, diagnostic device,measurement device, joint, screw, rod, ophthalmic implant, femoral pin,bone plate, graft, anastomotic device, perivascular wrap, suture,staple, shuntsfor hydrocephalus, dialysis graft, colostomy bagattachment device, ear drainage tube, lead for pace makers andimplantable cardioverters and defibrillators, vertebral disk, bone pin,suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascularimplant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmicimplant, prosthetic, shunt, urologic implant, reproductive anatomydevice, gastrologic device, neurologic lead, neurologic device, varioustypes of dressings (e.g., wound dressings), bone substitutes,intraluminal devices, and vascular supports.
 264. The device of claim261, wherein the layer is substantially impermeable to a gas.
 265. Thedevice of claim 261, wherein the layer is substantially impermeable to afluid.
 266. The device of claim 261, wherein the layer is substantiallyimpervious to a biological material.
 267. The device of claim 261,wherein the polymer is hydrophobic.
 268. The device of claim 261,wherein the polymer comprises at least one of a polyolefin, ametallocene polyolefins, a styrene polymers, a vinyl polymer, an acrylicpolymers, a polyester, a polyalkene, and a polyalkyne.
 269. The deviceof claim 261, wherein the polymer has a bulk density of at least about1.00 grams per cubic centimeter (g/cc).
 270. The device of claim 261,wherein polymer has a bulk density of greater than about 1.00 gram percubic centimeter (g/cc).
 271. The device of claim 261, wherein thepolymer has a bulk density of at least about one of 1.01, 1.02, 1.03,1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06,2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18,2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30,2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams percubic centimeter (g/cc).
 272. The device of claim 261, wherein the layerprovides a substantially conformal coating on the substrate.
 273. Thedevice of claim 261, wherein the layer provides a coating that issubstantially impermeable to leachants from the substrate.
 274. Thedevice of claim 261, wherein the layer provide a substantially conformalcoating on the substrate.
 275. The device of claim 261, comprising 5,10, 20, 50, or 100 layers of at least one of a polymer and annanoparticle.
 276. The device of claim 261, wherein the layer issubstantially defect-free.